Extracellular catalytic subunit activity of the cAMP-dependent protein kinase in prostate cancer

The role of cAMP in cell growth and differentiation, gene expression, and n euronal function is mediated by the cAMP-dependent protein kinase (PKA), Di fferential expression of type I and type II PKA has been correlated with ne oplastic tl transformation and differentiation, respectively. PKA is primar ily an intracellular enzyme. However, it has been demonstrated that PKA may be associated with the plasma membrane and is exposed to the extracellular environment. Here we report the first evidence for the presence of a free extracellular kinase activity of PKA in the growth media of cultured prosta te and other cancer cells, as well as in plasma samples from prostate cance r patients. This PKA activity is specific due to its phosphorylation of the PKA-specific substrate kemptide and its inhibition by the potent and speci fic PKA inhibitor PKI, but not by other protein kinase-inhibitory peptides, Intriguingly, this exoprotein kinase activity is cAMP independent, suggest ing that only the catalytic subunit is secreted, and therefore the kinase a ctivity is not modulated by the regulatory subunit of PKA. Western blot ana lysis of the culture supernatant from prostate cancer cells indicates the p resence of the catalytic subunit. This increase in extracellular PKA cataly tic subunit activity in prostate cancer may have profound effects on the tu morigenesis of prostate cancer and may serve as a novel marker and therapeu tic target for the disease.